Heijnen Chantal G M, Haenen Guido R M M, Oostveen R Minou, Stalpers Eva M, Bast Aalt
Faculty of Medicine, Department of Pharmacology and Toxicology, University of Maastricht, The Netherlands.
Free Radic Res. 2002 May;36(5):575-81. doi: 10.1080/10715760290025951.
The inhibition of the lipid peroxidation, induced by iron and ascorbate in rat liver microsomes, by phenols and flavones was studied. The activity of phenol was enhanced by electron donating substituents, denoted by the Hammett sigma (sigma). The concentration of the substituted phenols giving 50% inhibition (IC50) of lipid peroxidation gave a good correlation with the sigma of the substituent (ln(1/IC50) = -8.92sigma + 5.80 (R = 0.94, p < 0.05)). In flavones two pharmacophores for the protection against lipid peroxidation were pinpointed: (i) a catechol moiety as ring B and (ii) an OH-group at the 3 position with electron donating groups at the 5 and/or 7 position in the AC-ring. An example of a flavone with the latter pharmacophore is galangin (3,5,7-trihydroxyflavone) where the reactivity of the 3-OH-group is enhanced by the electron donating effect of the 5- and 7-OH-groups. This is comparable to the effect of electron donating substituents on the activity of phenol. The prooxidant activity of flavones has been related to a low half peak oxidation potential (Ep/2). All flavones with a catechol as ring B have very low Ep/2, suggesting that they display a prominent prooxidant activity. In contrast, the Ep/2 varies within the group of flavones with a 3-OH, e.g. TUM 8436 (5,7,3',4'-tetra-O-methyl-quercetin) has a relatively high Ep/2 and is an excellent protector against lipid peroxidation. Apparently amongst the flavones with the pharmacophore in the AC-ring there are good antioxidants that are expected to display no or limited prooxidant properties.
研究了酚类和黄酮类化合物对铁和抗坏血酸诱导的大鼠肝微粒体脂质过氧化的抑制作用。酚类的活性通过给电子取代基增强，用哈米特σ（sigma）表示。产生50%脂质过氧化抑制率（IC50）的取代酚浓度与取代基的σ具有良好的相关性（ln(1/IC50)= -8.92σ + 5.80（R = 0.94，p < 0.05））。在黄酮类化合物中，确定了两个防止脂质过氧化的药效基团：（i）作为B环的儿茶酚部分，以及（ii）A环和C环中5位和/或7位带有给电子基团的3位羟基。具有后一种药效基团的黄酮类化合物的一个例子是高良姜素（3,5,7-三羟基黄酮），其中3-OH基团的反应性因5-OH和7-OH基团的给电子作用而增强。这与给电子取代基对酚活性的影响相当。黄酮类化合物的促氧化活性与低半峰氧化电位（Ep/2）有关。所有以儿茶酚为B环的黄酮类化合物的Ep/2都非常低，表明它们具有显著的促氧化活性。相比之下，具有3-OH的黄酮类化合物组内的Ep/2有所不同，例如TUM 8436（5,7,3',4'-四-O-甲基槲皮素）具有相对较高的Ep/2，是一种出色的脂质过氧化保护剂。显然，在A环和C环具有药效基团的黄酮类化合物中，有一些良好的抗氧化剂，预计它们不会显示或仅具有有限的促氧化特性。
